Treatment of cancer using recall antigens delivered by attenuated bacteria

Abstract

Methods, pharmaceutical compositions and vaccines comprising an attenuated bacteria that expresses a recall antigen are disclosed for treatment of cancer.

1 . A method of treating a tumor in a subject, and/or reducing or preventing metastasis of a tumor in a subject, comprising administering to the subject an attenuated bacteria that expresses a recall antigen in an amount effective to treat the tumor, and/or to reduce or prevent metastasis of the tumor. 
     
     
         2 . The method of  claim 1 , wherein the bacteria is one or more of  Listeria monocytogenes, Salmonella thyphimurium, Vibrio cholera, Clostridium , and  Bifidobacterium breve.    
     
     
         3 . The method of  claim 1 , wherein the bacteria is  Listeria  monocytogenes. 
     
     
         4 . The method of  claim 1 , wherein the recall antigen is an epitope of one or more of tetanus toxoid, measle virus, and polio virus. 
     
     
         5 . The method of  claim 1 , wherein the recall antigen is an epitope of tetanus toxoid. 
     
     
         6 . The method of  claim 1 , wherein the tumor is a tumor of one or more of the pancreas, ovary, uterus, neck, head, breast, prostate, liver, lung, kidney, neurones, glia, colon, testicle, or bladder. 
     
     
         7 . The method of  claim 1 , wherein the tumor is an inoperable tumor. 
     
     
         8 . The method of  claim 1 , wherein prior to administration to the subject, the bacteria are cultured in yeast medium. 
     
     
         9 . The method of  claim 1 , which further comprises administering CpG to the subject. 
     
     
         10 . The method of  claim 1 , wherein prior to administration of bacteria to the subject, the subject is screened for their major histocompatibility complex (WIC) 1 haplotype and administered an antigen for which the subject shows a CD8 T cell recall response. 
     
     
         11 . The method of  claim 1 , wherein prior to administration of bacteria to the subject, an epitope of the antigen is administered to the subject to generate memory T cells to the antigen. 
     
     
         12 . The method of  claim 1 , wherein bacteria are administered systemically to the subject. 
     
     
         13 . The method of  claim 1 , wherein bacteria are administered by direct injection to a tumor site in the subject. 
     
     
         14 . The method of  claim 1 , wherein bacteria are administered in myeloid-derived suppressor cells (MDSCs). 
     
     
         15 . The method of  claim 1 , further comprising administering to the subject a chemotherapeutic agent that reduces the number of myeloid-derived suppressor cells (MDSCs). 
     
     
         16 . The method of  claim 15 , wherein the chemotherapeutic agent is gemcitabine. 
     
     
         17 . The method of  claim 1 , wherein the subject is a human. 
     
     
         18 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         19 . The method of  claim 1 , wherein the method is effective to reduce tumor growth and/or size. 
     
     
         20 . The method of  claim 1 , wherein the method is effective to reduce metastases.